Exploring antiviral effect and mechanism of Jinye Baidu granules（JYBD）against influenza A virus through network pharmacology and in vitro and invivo experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinye Baidu granules (JYBD) have been used to treat acute respiratory tract infections and demonstrated clinical efficacy for the treatment of emerging or epidemic respiratory viruses such as SARS-CoV-2 and influenza virus. AIM OF THE STUDY: This study is to investigate the antiviral effect of JYBD against influenza A viruses (IAV) in vitro and in vivo and elucidate its underlying mechanism. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography connected with Orbitrap mass spectrometer (UHPLC-Orbitrap MS) was employed to describe the chemical profile of JYBD. The potential pathways and targets involved in JYBD against IAV infection were predicted by network pharmacology. The efficacy and mechanism of JYBD were validated through both in vivo and in vitro experiments. Moreover, combination therapy with JYBD and the classic anti-influenza drugs was also investigated. RESULTS: A total of 126 compounds were identified by UHPLC-Orbitrap MS, of which 9 compounds were unambiguously confirmed with reference standards. JYBD could significantly inhibit the replication of multiple strains of IAV, especially oseltamivir-resistant strains. The results of qRT-PCR and WB demonstrated that JYBD could inhibit the excessive induction of pro-inflammatory cytokines induced by IAV infection and regulate inflammatory response through inhibiting JAK/STAT, NF-κB and MAPK pathways. Moreover, both JYBD monotherapy or in combination with oseltamivir could alleviate IAV-induced severe lung injury in mice. CONCLUSIONS: JYBD could inhibit IAV replication and mitigate virus-induced excessive inflammatory response. Combinations of JYBD and neuraminidase inhibitors conferred synergistic suppression of IAV both in vitro and in vivo. It might provide a scientific basis for clinical applications of JYBD against influenza virus infected diseases.

Clinical efficacy of enhanced recovery surgery in Da Vinci robot-assisted pancreatoduodenectomy.

Da Vinci robot-assisted pancreaticoduodenectomy offers advantages, including minimal invasiveness, precise, and safe procedures. This study aimed to investigate the clinical effectiveness of implementing enhanced recovery after surgery (ERAS) concepts in Da Vinci robot-assisted pancreaticoduodenectomy. A retrospective analysis was conducted on clinical data from 62 patients who underwent Da Vinci robot-assisted pancreaticoduodenectomy between January 2018 and December 2022. Among these patients, 30 were managed with ERAS principles, while 32 were managed using traditional perioperative management protocols. Surgical time, intraoperative blood loss, postoperative oral intake time, time to return of bowel function, time to ambulation, visual analog scale (VAS) pain scores, fluid replacement volume, length of hospital stay, total hospital expenses, complications, and patient satisfaction were recorded and compared between the two groups. Postoperative follow-up included assessment of postoperative functional scores, reoperation rates, SF-36 quality of life scores, and survival rates. The average follow-up time was 35.6 months (range: 12-56 months). There were no statistically significant differences in general characteristics, including age, surgical time, intraoperative blood loss, and preoperative medical history between the two groups (P > 0.05). Compared to the control group, the intervention group had an earlier postoperative oral intake time, faster return of bowel function, rapid ambulation, and shorter hospital stays (P < 0.05). The intervention group also had lower postoperative VAS scores, lower fluid replacement volume, lower total hospital expenses, and a lower rate of complications (P < 0.05). Patient satisfaction was higher in the intervention group (P < 0.05). There were no statistically significant differences between the two groups in two-year functional scores, reoperation rates, quality of life scores, and survival rates (P > 0.05). Implementing ERAS principles in Da Vinci robot-assisted pancreaticoduodenectomy substantially expedited postoperative recovery, lowered pain scores, and diminished complications. However, there were no notable differences in long-term outcomes between the two groups.

Spatial analysis of the impact of urban built environment on cardiovascular diseases: a case study in Xixiangtang, China.

BACKGROUND: The built environment, as a critical factor influencing residents' cardiovascular health, has a significant potential impact on the incidence of cardiovascular diseases (CVDs). METHODS: Taking Xixiangtang District in Nanning City, Guangxi Zhuang Autonomous Region of China as a case study, we utilized the geographic location information of CVD patients, detailed road network data, and urban points of interest (POI) data. Kernel density estimation (KDE) and spatial autocorrelation analysis were specifically employed to identify the spatial distribution patterns, spatial clustering, and spatial correlations of built environment elements and diseases. The GeoDetector method (GDM) was used to assess the impact of environmental factors on diseases, and geographically weighted regression (GWR) analysis was adopted to reveal the spatial heterogeneity effect of environmental factors on CVD risk. RESULTS: The results indicate that the built environment elements and CVDs samples exhibit significant clustering characteristics in their spatial distribution, with a positive correlation between the distribution density of environmental elements and the incidence of CVDs (Moran's I > 0, p < 0.01). Further factor detection revealed that the distribution of healthcare facilities had the most significant impact on CVDs (q = 0.532, p < 0.01), followed by shopping and consumption (q = 0.493, p < 0.01), dining (q = 0.433, p < 0.01), and transportation facilities (q = 0.423, p < 0.01), while the impact of parks and squares (q = 0.174, p < 0.01) and road networks (q = 0.159, p < 0.01) was relatively smaller. Additionally, the interaction between different built environment elements exhibited a bi-factor enhancement effect on CVDs. In the local analysis, the spatial heterogeneity of different built environment elements on CVDs further revealed the regional differences and complexities. CONCLUSIONS: The spatial distribution of built environment elements is significantly correlated with CVDs to varying degrees and impacts differently across regions, underscoring the importance of the built environment on cardiovascular health. When planning and improving urban environments, elements and areas that have a more significant impact on CVDs should be given priority consideration.

Hydrogen sulfide inhibits skeletal muscle ageing by up-regulating autophagy through promoting deubiquitination of adenosine 5'-monophosphate (AMP)-activated protein kinase α1 via ubiquitin specific peptidase 5.

BACKGROUND: Hydrogen sulfide (H2S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H2S alleviates skeletal muscle ageing by regulating autophagy has not been reported. METHODS: Mice were administered 150 mg/kg/day of D-galactose ( D-gal), and C2C12 myotubes were cultured in 20 g/L D-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H2S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot. RESULTS: NaHS was found to effectively restore the H2S content in both ageing gastrocnemius (+91.89%, P < 0.001) and C2C12 myotubes (+27.55%, P < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, P < 0.001), to decrease the collagen volume fraction of gastrocnemius (-81.32%, P = 0.001) and to reduce the ß-galactosidase-positive area of C2C12 myotubes (-28.74%, P < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: -31.73%, P = 0.008; MuRF1: -32.37%, P = 0.003; Cyclin D1: +45.34%, P = 0.010; p21: -25.53%, P = 0.022) and C2C12 myotubes (MAFbx: -16.38%, P < 0.001; MuRF1: -16.45%, P = 0.003; Cyclin D1: +40.23%, P < 0.001; p21: -35.85%, P = 0.026). The AMPKα1-ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, P = 0.018; AMPKα1: +30.64%, P = 0.010; p-ULK1/ULK1: +85.87%, P = 0.005; p62: -29.07%, P < 0.001; Beclin1: +24.75%, P = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, P = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, P = 0.018; AMPKα1: +26.18%, P = 0.022; p-ULK1/ULK1: +38.34%, P = 0.012; p62: -9.02%, P = 0.014; Beclin1: +13.36%, P < 0.001; LC3 II/I: +79.38%, P = 0.017; autophagy flux: +24.88%, P = 0.034) compared with the D-gal group. The effects of NaHS on autophagy were comparable to those of acadesine and LYN-1604, and chloroquine could reverse its effects on ageing. LC-MS/MS and Co-IP experiments demonstrated that USP5 is a deubiquitinating enzyme of AMPKα1. Following the knockdown of USP5, the activation of AMPKα1 was decreased (p-AMPKα1: -42.10%, P < 0.001; AMPKα1: -43.93%, P < 0.001), autophagy was inhibited (p-ULK1/ULK1: -27.51, P = 0.001; p62: +36.00, P < 0.001; Beclin1: -22.15%, P < 0.001) and NaHS lost its ability to up-regulate autophagy. NaHS was observed to restore the expression (gastrocnemius: +62.17%, P < 0.001; C2C12 myotubes: +37.51%, P = 0.003) and S-sulfhydration (+53.07%, P = 0.009) of USP5 and reduce the ubiquitination of AMPKα1. CONCLUSIONS: H2S promotes the deubiquitination of AMPKα1 by increasing the expression and S-sulfhydration of USP5, thereby up-regulating autophagy and alleviating skeletal muscle ageing.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Development and biomechanical analysis of an axially controlled compression spinal rod for lumbar spondylolysis.

BACKGROUND: To elucidate the differences in mechanical performance between a novel axially controlled compression spinal rod (ACCSR) for lumbar spondylolysis (LS) and the common spinal rod (CSR). METHODS: A total of 36 ACCSRs and 36 CSRs from the same batch were used in this study, each with a diameter of 6.0 mm. Biomechanical tests were carried out on spinal rods for the ACCSR group and on pedicle screw-rod internal fixation systems for the CSR group. The spinal rod tests were conducted following the guidelines outlined in the American Society for Testing and Materials (ASTM) F 2193, while the pedicle screw-rod internal fixation system tests adhered to ASTM F 1798-97 standards. RESULTS: The stiffness of ACCSR and CSR was 1559.15 ±â€…50.15 and 3788.86 ±â€…156.45 N/mm (P < .001). ACCSR's yield load was 1345.73 (1297.90-1359.97) N, whereas CSR's was 4046.83 (3805.8-4072.53) N (P = .002). ACCSR's load in the 2.5 millionth cycle of the fatigue four-point bending test was 320 N. The axial gripping capacity of ACCSR and CSR was 1632.53 ±â€…165.64 and 1273.62 ±â€…205.63 N (P = .004). ACCSR's torsional gripping capacity was 3.45 (3.23-3.47) Nm, while CSR's was 3.27 (3.07-3.59) Nm (P = .654). The stiffness of the pedicle screws of the ACCSR and CSR group was 783.83 (775.67-798.94) and 773.14 (758.70-783.62) N/mm (P = .085). The yield loads on the pedicle screws of the ACCSR and CSR group was 1345.73 (1297.90-1359.97) and 4046.83 (3805.8-4072.53) N (P = .099). CONCLUSION: Although ACCSR exhibited lower yield load, stiffness, and fatigue resistance compared to CSR, it demonstrated significantly higher axial gripping capacity and met the stress requirement of the human isthmus. Consequently, ACCSR presents a promising alternative to CSR for LS remediation.

Identification of candidate genes for Fusarium head blight resistance from QTLs using RIL population in wheat.

Fusarium head blight (FHB) stands out as one of the most devastating wheat diseases and leads to significantly grain yield losses and quality reductions in epidemic years. Exploring quantitative trait loci (QTL) for FHB resistance is a critical step for developing new FHB-resistant varieties. We previously constructed a genetic map of unigenes (UG-Map) according to the physical positions using a set of recombinant-inbred lines (RILs) derived from the cross of 'TN18 × LM6' (TL-RILs). Here, the number of diseased spikelets (NDS) and relative disease index (RDI) for FHB resistance were investigated under four environments using TL-RILs, which were distributed across 13 chromosomes. A number of 36 candidate genes for NDS and RDI from of 19 stable QTLs were identified. The average number of candidate genes per QTL was 1.89, with 14 (73.7%), two (10.5%), and three (15.8%) QTLs including one, two, and 3-10 candidate genes, respectively. Among the 24 candidate genes annotated in the reference genome RefSeq v1.1, the homologous genes of seven candidate genes, including TraesCS4B02G227300 for QNds/Rdi-4BL-4553, TraesCS5B02G303200, TraesCS5B02G303300, TraesCS5B02G303700, TraesCS5B02G303800 and TraesCS5B02G304000 for QNds/Rdi-5BL-9509, and TraesCS7A02G568400 for QNds/Rdi-7AL-14499, were previously reported to be related to FHB resistance in wheat, barely or Brachypodium distachyon. These genes should be closely associated with FHB resistance in wheat. In addition, the homologous genes of five genes, including TraesCS1A02G037600LC for QNds-1AS-2225, TraesCS1D02G017800 and TraesCS1D02G017900 for QNds-1DS-527, TraesCS1D02G018000 for QRdi-1DS-575, and TraesCS4B02G227400 for QNds/Rdi-4BL-4553, were involved in plant defense responses against pathogens. These genes should be likely associated with FHB resistance in wheat.

Synchronous Double Primary Tumors of Liver (Small Cell Neuroendocrine Carcinoma and Hepatocellular carcinoma): A Case Report.

This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII-VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII-VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient's survival time was 16 months.

Heterochronous multiple primary prostate cancer and lymphoma: A case report.

BACKGROUND: Multiple primary malignant tumors (MPMTs) are rare type of cancer, especially when solid tumors are the first and lymphoma is the second primary malignancy. We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma (DLBCL). CASE SUMMARY: We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide (50 mg per day) and an extended-release implant of goserelin (1/28 d). Seven years later, rectal DLBCL with lung metastases was found. CONCLUSION: Although rare, the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.

Top 100 cited articles in the thromboangiitis obliterans: a bibliometric analysis and visualized study.

OBJECTIVE: Thromboangiitis obliterans (TAO) is one of the most common types of peripheral arterial disease (PAD). This study aimed to explore the characteristics of the top 100 most cited articles in the TAO. METHODS: A bibliometric analysis based on the Web of Science (WOS) database was performed. Literature was retrieved and ranked by the citations. Listed below are the top 100 citations, including original articles, reviews, full-length proceeding papers, and case reports that were included for analysis. The type of literature, research areas, and languages were recorded. The trends of citations including the total citations, an analysis of publication and citation numbers were conducted each year. We analyzed citations from highly cited countries, authors, institutions, and journals. Research hotspots were gathered by a visualized analysis of author keywords. RESULTS: Most of the highly cited literature was original articles. A rising trend was observed in the number of citations per year. The peaks in the number of highly cited articles appeared in the year 1998 and 2006. The majority of the articles focused on the cardiovascular system and surgery. Journal of Vascular Surgery published most of the highly cited articles. The USA and Japan contributed nearly half the number of highly cited articles. Mayo Clinic and Nagoya University were highly cited institutions. Shionoya S and Olin JW were both the author with the largest number of citations and the most highly cited author in the reference. Articles that were highly cited most often addressed the following topics: "vasculitis", "autoimmune disease", and "critical limb ischemia". Keywords that were mostly used in recent years were "stem cell therapy", "progenitor therapy", and "immunoadsorption". The detection of bursts of author keywords showed the following: "permeability", "differentiation", and "critical limb ischemia" are recent keywords that have burst. CONCLUSIONS: In this study, the highly cited contributors in the field of TAO research were identified. Most cited articles in the top 100 focused on the cardiovascular system and surgery. Treatment and pathophysiology including stem cell therapy, progenitor therapy, genetics, autoimmunity, and inflammation are the hotspots of TAO.

Gefitinib, an effective treatment option for patients with pulmonary enteric adenocarcinoma harboring compound EGFR L858R and A871G mutation.

Pulmonary enteric adenocarcinoma (PEAC) is a rare lung adenocarcinoma with morphological and immunohistochemical similarities to colorectal adenocarcinoma and intestinal differentiation. PEAC belongs to the group of non-small-cell lung carcinoma (NSCLC) and is defined as having a more than 50% intestinal differentiation component. We report a postoperative (T4N2M0 stage IIIb) PEAC patient with EGFR L858R + A871G combined mutation. Following surgery, the patient underwent treatment with the first-generation EGFR-TKI, gefitinib, and achieved an impressive 5-year progression-free survival (PFS). This suggests that gefitinib may serve as an effective treatment option for PEAC patients with EGFR L858R + A871G compound mutations.

Incidence of lumbar spondylolysis in athletes with low back pain: A systematic evaluation and single-arm meta-analysis.

BACKGROUND: Low back pain (LBP) is a common chief complaint from athletes. Lumbar spondylolysis (LS) is a common sport injury. Severe LS is likely to cause spinal instability, resulting in lumbar spondylolisthesis or lumbar disc herniation, and even damage to the spinal nerve roots. The incidence of LS is approximately 5% in the adult population, and nearly half of young athletes with LBP are diagnosed with LS. This meta-analysis analyzed the incidence of LS in athletes with LBP. METHODS: PubMed, Embase, Cochrane (Cochrane Central Register of Controlled Trials), and Web of Science databases were systematically searched for published case report and retrospective analyses related to the topic from the date of database creation to January 1,2023. Relevant literature was screened and information extracted, and risk of bias was assessed for included studies using the methodological index for non-randomized-studies scale. Single-arm Meta-analysis was performed using R4.04 software. Heterogeneity was quantified by Cochran Q test and Higgins I2. Funnel plots were used to visualize publication bias, and Egger test and Begg test were used to statistical tests. RESULTS: A total of 9 studies (835 patients) were included in this study. Meta-analysis revealed that the prevalence of LS in athletes with LBP was estimated at 41.7%, [95% CI = (0.28-0.55)], but this prevalence varied considerably with the gender and age of the athletes. CONCLUSION: The estimated prevalence of LS in athletes with LBP is 41.7%, and future correlations between the prevalence of LS in adolescent athletes worldwide need to be assessed from different perspectives, including biomechanical, hormonal, anatomical, behavioral, and gender differences.

Development and validation of prognostic nomogram for patients with metastatic gastric adenocarcinoma based on the SEER database.

The aim of this study was to investigate the prognostic factors affecting overall survival in patients with metastatic gastric adenocarcinoma and to establish a nomogram prediction model for comprehensive clinical application. Data from 2370 patients with metastatic gastric adenocarcinoma between 2010 and 2017 were retrieved from the surveillance, epidemiology, and end results database. They were randomly divided into a training set (70%) and a validation set (30%), univariate and multivariate Cox proportional hazards regressions were used to screen important variables that may affect overall survival and to establish the nomogram. The nomogram model was evaluated using a receiver operating characteristic curve, calibration plot, and decision curve analysis. Internal validation was performed to test the accuracy and validity of the nomogram. Univariate and multivariate Cox regression analyses revealed that, age, primary site, grade, and American joint committee on cancer. T, bone metastasis, liver metastasis, lung metastasis, tumor Size, and chemotherapy were identified as independent prognostic factors for overall survival and were included in the prognostic model to construct a nomogram. The prognostic nomogram showed good overall survival risk stratification ability for the area under the curve, calibration plots, and decision curve analysis in both the training and validation sets. Kaplan-Meier curves further showed that patients in the low-risk group had better overall survival. This study synthesizes the clinical, pathological, therapeutic characteristics of patients with metastatic gastric adenocarcinoma, establishes a clinically effective prognostic model, and that can help clinicians to better evaluate the patient's condition and provide accurate treatment.

Potential Role of Superoxide Dismutase 3 (SOD3) in Resistance to Influenza A Virus Infection.

Influenza A virus infection induces the production of excessive reactive oxygen species (ROS). Overproduction of ROS can overwhelm the antioxidant defense system, leading to increasing intensive oxidative stress. However, antioxidant defense against oxidative damage induced by influenza A virus infection, and in particular the significance of the SOD3 response in the pathogenesis of influenza virus infection, has not been well characterized. Here, we investigated the potential role of SOD3 in resistance to influenza A virus infection. In this study, SOD3, as an important antioxidant enzyme, was shown to be highly elevated in A549 cells following influenza A virus infection. Furthermore, inhibition of SOD3 impacted viral replication and virulence. We found that SOD3 disrupts IAV replication by impairing the synthesis of vRNA, whereas it did not affect viral ribonucleoprotein nuclear export. In addition, overexpression of SOD3 greatly reduced the levels of ROS caused by influenza A virus infection, regulated the inflammatory response to virus infection by inhibiting the phosphorylation of p65 of the NF-κB signaling pathway, and inhibited virus-induced apoptosis to a certain extent. Taken together, these findings indicate that SOD3 is actively involved in influenza A virus replication. Pharmacological modulation or targeting of SOD3 may pave the way for a novel therapeutic approach to combating influenza A virus infection.

Nisoldipine Inhibits Influenza A Virus Infection by Interfering with Virus Internalization Process.

Influenza virus infections and the continuing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are global public health concerns. As there are limited therapeutic options available in clinical practice, the rapid development of safe, effective and globally available antiviral drugs is crucial. Drug repurposing is a therapeutic strategy used in treatments for newly emerging and re-emerging infectious diseases. It has recently been shown that the voltage-dependent Ca2+ channel Cav1.2 is critical for influenza A virus entry, providing a potential target for antiviral strategies. Nisoldipine, a selective Ca2+ channel inhibitor, is commonly used in the treatment of hypertension. Here, we assessed the antiviral potential of nisoldipine against the influenza A virus and explored the mechanism of action of this compound. We found that nisoldipine treatment could potently inhibit infection with multiple influenza A virus strains. Mechanistic studies further revealed that nisoldipine impaired the internalization of the influenza virus into host cells. Overall, our findings demonstrate that nisoldipine exerts antiviral effects against influenza A virus infection and could serve as a lead compound in the design and development of new antivirals.

The Landscape of Early Growth Response Family Members 1-4 in Hepatocellular Carcinoma: Their Biological Roles and Diagnostic Utility.

The incidence of hepatocellular carcinoma (HCC), which is one of the most frequent types of cancer seen all over the world, is steadily growing from year to year. EGR genes are members of the early growth response (EGR) gene family. It has been shown that EGR genes play an increasingly essential role in the development of tumors and the progression of numerous malignancies. However, the possible diagnostic and prognostic roles of EGR genes in HCC have only been examined in a limited number of studies. Expression and methylation data on EGR family members were obtained from TCGA datasets. The prognostic values of EGR members were studied. Additionally, the correlations of EGR members with immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA). In this study, we found that the expression of EGR1, EGR2, EGR3, and EGR4 was distinctly decreased in HCC specimens compared with nontumor specimens. ROC assays confirmed that they have a strong ability in screening HCC specimens from nontumor specimens. According to the findings of Pearson's correlation, EGR1, EGR2, EGR3, and EGR4 were found to have a negative association with the methylation level. Survival study revealed that EGR1, EGR2, and EGR3 were associated with the clinical outcome of HCC patients. Immune cell enrichment analysis demonstrated that the expressions of all EGR members were positively related to the levels of most types of immune cells, such as macrophages, NK cells, B cells, T cells, eosinophils, and CD8 T cells. Overall, the current work demonstrated the expression mode and prognostic value of EGR members in HCC in a comprehensive manner, offering insights for further research of the EGR family as possible clinical biomarkers in HCC.

Treatment of inferior pole fracture of the patella with tension-free external immobilization.

BACKGROUND: Inferior pole fracture of the patella (IPFP) has small and comminuted fracture blocks that are hard to immobilize, and early mobilization may lead to loss of fracture reduction and immobilization failure. Therefore, a difficulty of treatment is to achieve rigid immobilization with early functional exercise. Here, a new treatment method of tension-free external immobilization is put forward. METHODS: The clinical data of 11 IPFP patients treated with tension-free external immobilization from May 2016 to June 2019 were retrospectively analyzed. There were six males and five females aged 39.0 ± 12.8 years (range 18-53 years). IPFP was caused by traffic accidents in five cases and falls in six cases. All cases had unilateral closed injuries, including four in the left knee and seven in the right knee. The preoperative range of motion of the knee was 22.0 ± 7.5° (10-30°). The time from injury to operation was 4.5 ± 1.3 d (3-7 d). The operation-related indices were recorded, and the function of the affected knee was assessed by the Böstman score. RESULTS: All operations were successful. The operation time was 56.4 ± 8.4 mi (45-70 min), the intraoperative blood loss was 54.1 ± 14.6 mL (40-80 mL), and the length of hospital stay was 7.5 ± 1.9 d (5-11 d). The mean follow-up time was 20.4 ± 7.6 months (12-36 months), the duration of fracture healing was 8.9 ± 1.5 weeks (7-12 weeks), and the removal time of the external immobilization device was 10.4 ± 0.9 weeks (9-12 weeks). At the last follow-up, the range of motion had no significant difference between the affected knee (129.7 ± 3.3°, range 125-135°) and the unaffected knee (130.8 ± 3.8°, range 126-137°) (t = 0.718, p < 0.05). The Böstman score of the knee was 29.2 ± 1.0 points (27-30 points), including 10 excellent cases (90.9%) and one good case (9.1%). CONCLUSION: Tension-free external immobilization is a feasible treatment for IPFP. It can help with early functional exercise and achieve a satisfactory clinical effect.

Feasibility of cortical bone trajectory screws for bridging fixation in revision surgery for lumbar adjacent segment degeneration.

BACKGROUND: To investigate the feasibility of using cortical bone trajectory (CBT) screws for bridging fixation in revision surgery for lumbar adjacent segment degeneration and to provide a reference for clinical practice. METHODS: Computed tomography scans of the lumbar spines of 36 patients in our hospital were used. Sixteen males and 20 females with an average age of 65.5 ±â€Š10.5 years (range: 46 to 83 years) were included. Three-dimensional reconstruction was performed using computer software. Screws with appropriate sizes were selected for the L1 to L5 vertebral segments, and traditional pedicle screws were placed using the standard method. After completing screw placement, simulated placement of CBT screws was performed separately. No overlap occurred between the two screws in the process of CBT screw placement, and the placement point and direction were adjusted until screw placement completion. After all screw placement simulations were complete, according to the contact area of the cortical bone of the screw trajectory and the screw puncture position and distance through the trajectory, the screw placement results were categorized as excellent, good, general, and failure. Excellent and good ratings were considered successful, while a general rating was regarded as acceptable. Then, the success rate and acceptable rate of each segment of the lumbar spine were calculated. RESULTS: Three hundred and sixty screw placement simulations were performed in lumbar pedicles, and 72 CBT screws were implanted in each vertebral body of the lumbar spine. The success rates in the L1 to L5 segments were 73.6%, 80.6%, 83.3%, 88.9%, and 77.8%, respectively, and the acceptable rates were 91.7%, 97.2%, 97.2%, 100%, and 91.7%, respectively. The overall success rate and acceptable rate of CBT screw placement in the lumbar spine were 80.8% and 95.6%, respectively. CONCLUSION: CBT screws are feasible for bridging fixation in lumbar adjacent segment degeneration revision surgery, and the accuracy of screw placement in different lumbar vertebrae varies.

Double-trajectory lumbar screw placement guided by a set of 3D-printed surgical guide templates: a cadaver study.

BACKGROUND: To improve the strength of posterior spine fixation in patients with osteoporosis, some scholars have proposed a method of simultaneously inserting traditional pedicle screws and cortical bone trajectory screws into the pedicle. However, due to the difficulty of the operation and few clinical applications, the safety and accuracy of this method are still unclear. The purpose of this study was to investigate the safety and accuracy of double-trajectory lumbar screw placement guided by surgical guide templates. METHODS: Six wet lumbar specimens were selected for computed tomography (CT) scanning, a three-dimensional (3D) model of the lumbar spine was established using computer software, and surgical guide templates for double-trajectory [traditional pedicle trajectory (TPT) and cortical bone trajectory (CBT)] lumbar screw placement at various segments of the lumbar spine were designed and printed using a 3D printer. Screw placement was guided only by the surgical guide template, with no fluoroscopy. Postoperative CT examination was performed to determine whether the screw penetrated the screw path and the location and depth of penetration of the cortex. The preoperative and postoperative sagittal and axial angles of CBT screws or TPT screws were also measured and compared. RESULTS: Four screws were placed in each vertebral body of six lumbar specimens for a total of 120 screws. Screw grades: 99 screws as grade 0, 15 as grade 1, six as grade 2, and zero as grade 3. Thus, grade 0 accounted for 82.5% of the screws. No significant differences in the preoperative and postoperative angles of the screws were found (P > 0.05). CONCLUSIONS: 3D-printed surgical guide templates for double-trajectory screw placement can reduce the difficulty of surgery and the use of intraoperative fluoroscopy. Using such templates is a safe, feasible, and accurate screw placement method.

Anatomical study of the ideal cortical bone trajectory in the lumbar spine.

BACKGROUND: To explore the ideal trajectory of lumbar cortical bone trajectory screws and provide the optimal placement scheme in clinical applications. METHODS: Lumbar computed tomography (CT) data of 40 patients in our hospital were selected, and the cortical vertebral bone contour model was reconstructed in three dimensions (3D). Depending on the different regions of the screw through the entrance and exit of the pedicle, 9 trajectories were obtained through combinational design: T-Aa, T-Ab, T-Ac, T-Ba, T-Bb, T-Bc, T-Ca, T-Cb, and T-Cc. Cortical bone trajectory (CBT) screws with appropriate diameters were selected to simulate screw placement and measure the parameters corresponding to each trajectory (screw path diameter, screw trajectory length, cephalad angle, and lateral angle), and then determine the optimal screw according to the screw parameters and screw safety. Then, 23 patients in our hospital were selected, and the navigation template was designed based on the ideal trajectory before operation, CBT screws were placed during the operation to further verify the safety and feasibility of the ideal trajectory. RESULTS: T-Bc and T-Bb are the ideal screw trajectories for L1-L2 and L3-L5, respectively. The screw placement point is located at the intersection of the inner 1/3 vertical line of the superior facet joint and the bottom 1/3 horizontal line of the outer crest of the vertebral lamina (i.e., 2-4 mm inward at the bottom 1/3 of the outer crest of the vertebral lamina). CBT screws were successfully placed based on the ideal screw trajectory in clinical practice. During the operation or the follow-up period, there were no adverse events. CONCLUSION: CBT screw placement based on the ideal screw trajectory is a safe and reliable method for achieving effective fixation and satisfactory postoperative effects.